Study Type 1 (Closed Environment Studies) PROJECT SUMMARY Evaluation of Spatial Repellents against Pyrethroid-Resistant Malaria Vectors in MalariaSpheres Many alternative malaria vector control methods have been the subject of research studies over the past two decades. Among the potential tools, repellents have received the largest attention from industry. Spatial repellents release volatile active ingredients into the surrounding air that interfere with the ability of mosquitoes to locate human host, thus conferring protection from mosquito bites through the action of emanated vapor or airborne chemical particles in a large space. Most spatial repellents use pyrethroids as the major volatile to repel mosquitoes. These repellents prevent mosquitoes from entering houses, induce early exit, and reduce human biting. Currently existing evidence on the efficacy of spatial repellents comes mainly from pyrethroid- susceptible mosquitoes. Because African malaria vectors are now showing widespread pyrethroid resistance, it is important to know whether spatial repellents work well against the resistant mosquitoes. The central objective of this proposal is to examine the impact of spatial repellents being marketed in Kenya and Ethiopia and novel repellents on the behavioral response of pyrethroid-resistant African malaria mosquitoes. We propose two specific aims: 1) Evaluate the effect of spatial repellent products that are being sold in Kenya and Ethiopia on preventing pyrethroid- resistant mosquitoes from approaching houses and from house entry in semi-field contained MalariaSpheres, and 2) Examine house entry and exiting behavior of pyrethroid-resistant malaria vectors that have a high tendency to perform outdoor biting in MalariaSpheres using video-recorded flight track 3D analysis and swarm intelligence simulation, which simulates flight behavior in a swarm of mosquitoes. This project will provide evidence to determine whether spatial repellents available on the local market in Africa repel local malaria vectors that are pyrethroid-resistant and adapted to outdoor biting. The information and knowledge obtained from this project will be useful for guiding the public toward understanding whether spatial repellents on local markets are useful for preventing malaria transmission, and will be valuable to mosquito repellent product developers to help them determine appropriate chemical compounds and dosage for their repellents against pyrethroid-resistant African malaria mosquitoes. The project is timely due to increasing and widespread pyrethroid resistance of African malaria vectors.